Optic nerve damage in shaken baby syndrome: detection by beta-amyloid precursor protein immunohistochemistry

BACKGROUND: Rapid acceleration-deceleration of an infant's head during intentional shaking should in theory exert stretch or shear forces upon the optic nerves sufficient to cause axonal injury. beta-Amyloid precursor protein (beta-APP) immunohistochemistry recently has been shown to be a highly effective method for identifying diffuse axonal injury in the brains of infants with shaken baby syndrome. In this study, we investigated the utility of beta-APP in identifying optic nerve damage in infants who have sustained fatal whiplash shaking. MATERIALS AND METHODS: beta-Amyloid precursor protein immunohistochemistry was performed on formalin-fixed, paraffin-embedded sections of eyes (including optic disc and distal optic nerve) from infants less than 1 year of age with shaken baby syndrome (5 cases), combined shaken baby syndrome/blunt head trauma (3 cases), and "pure" blunt head trauma (1 case). Nontraumatic control cases included infants who died of suffocation (1 case), sudden infant death syndrome (1 case), and positional asphyxia (1 case) and an enucleation from a child with a retinoblastoma (1 case). Matched hematoxylin-eosin-and neurofilament-stained sections were used for comparison. RESULTS: Three of the 5 shaken baby cases and all 3 combined shaken baby/blunt head trauma cases had optic nerve axonal injury identified by the presence of strongly beta-APP-immunoreactive beaded or swollen axonal segments. Axonal injury could not be detected in the corresponding hematoxylin-eosin-or neurofilament-stained sections. Optic nerve axonal injury was not seen in the case involving pure blunt head trauma or in the nontraumatic control cases. CONCLUSIONS: Optic nerve axonal injury is a prominent feature of intentional fatal whiplash head trauma in infants less than 1 year of age. beta-Amyloid protein precursor immunohistochemistry appears to be the most effective method for demonstrating axonal damage in the optic nerve.     

Diffuse axonal injury in infants with nonaccidental craniocerebral trauma: enhanced detection by beta-amyloid precursor protein immunohistochemical staining

OBJECTIVE: Accurate identification of diffuse axonal injury is important in the forensic investigation of infants who have died from traumatic brain injury. beta-Amyloid precursor protein (beta-APP) immunohistochemical staining is highly sensitive in identifying diffuse axonal injury. However, the effectiveness of this method in brain-injured infants has not been well established. The present study was undertaken to assess the utility of beta-APP immunohistochemistry in detecting diffuse axonal injury in infants with either shaken baby syndrome or blunt head trauma. MATERIALS AND METHODS: Archival formalin-fixed, paraffin-embedded blocks from infants (<1 year old) with shaken baby syndrome (7 cases) and blunt head trauma (3) and blocks from 7 control cases that included nontraumatic cerebral edema (1), acute hypoxic-ischemic encephalopathy (1), and normal brain (5) were immunostained for beta-APP. A semiquantitative assessment of the severity of axonal staining was made. Corresponding hematoxylin-eosin-stained sections were examined for the presence of axonal swellings. RESULTS: Immunostaining for beta-APP identified diffuse axonal injury in 5 of 7 infants with shaken baby syndrome and 2 of 3 infants with blunt head trauma. Immunoreactive axons were easily identified and were present in the majority of the sections examined. By contrast, hematoxylineosin staining revealed axonal swellings in only 3 of 7 infants with shaken baby syndrome and 1 of 3 infants with blunt head trauma. Most of these sections had few if any visible axonal swellings, which were often overlooked on initial review of the slides. No beta-APP immunoreactivity was observed in any of the 7 control cases. CONCLUSIONS: Immunostaining for beta-APP can easily and reliably identify diffuse axonal injury in infants younger than 1 year and is considerably more sensitive than routine hematoxylin-eosin staining. We recommend its use in the forensic evaluation of infants with fatal craniocerebral trauma.     

The child as a projectile

Unintentional injury is the leading cause of death in children under the age of fourteen. The majority of these injuries/deaths occur when the child becomes airborne during an accident. The most common mechanisms by which children become airborne are motor vehicle collisions, bicycling accidents, and falls. A head injury is seen in a significant number of children in this setting. This includes injury to the scalp, skull, coverings of the brain, or the brain itself. These injuries are the most common cause of death in children resulting from unintentional injury. Other typical injuries include external bruises and abrasions, extremity fractures, and bruising or bleeding of internal organs. We propose to name this constellation of injuries the projectile child syndrome. This refers to those injuries occurring in infants and children as a result of becoming airborne during the events of an accident. The pattern of injuries seen as related to the anatomy of the child is stressed. A review of the impact to society and guidelines for prevention are presented. Anat. Rec. (New Anat.) 253:167–175, 1998. © 1998 Wiley-Liss, Inc.     

Delayed white matter injury in a murine model of shaken baby syndrome

Shaken baby syndrome, a rotational acceleration injury, is most common between 3 and 6 months of age and causes death in about 10 to 40% of cases and permanent neurological abnormalities in survivors. We developed a mouse model of shaken baby syndrome to investigate the pathophysiological mechanisms underlying the brain damage. Eight-day-old mouse pups were shaken for 15 seconds on a rotating shaker. Animals were sacrificed at different ages after shaking and brains were processed for histology. In 31-day-old pups, mortality was 27%, and 75% of survivors had focal brain lesions consisting of hemorrhagic or cystic lesions of the periventricular white matter, corpus callosum, and brainstem and cerebellar white matter. Hemorrhagic lesions were evident from postnatal day 13, and cysts developed gradually between days 15 and 31. All shaken animals, with or without focal lesions, had thinning of the hemispheric white matter, which was significant on day 31 but not earlier. Fragmented DNA labeling revealed a significant increase in cell death in the periventricular white matter, on days 9 and 13. White matter damage was reduced by pre-treatment with the NMDA receptor antagonist MK-801. This study showed that shaking immature mice produced white matter injury mimicking several aspects of human shaken baby syndrome and provided evidence that excess release of glutamate plays a role in the pathophysiology of the lesions.     

Intracranial diffuse axonal injury at autopsy

An illustrative case of diffuse axonal injury (DAI) emphasizes features that help to separate focal outer head trauma owing to blows and/or falls from angular acceleration head injuries associated with diffuse inner brain lesions. In the past, explaining significant neurological deficits and death as the result of diffuse closed head trauma received from high-speed automobile accidents has been difficult as well as confusing. The long-term consequences from such diffuse inner cerebral trauma are still poorly defined. Head injuries sustained in automobile accidents have been associated with diffuse brain damage characterized by axonal injury at the moment of impact. The reported victim of a motor vehicle accident showed post-mortem findings for both inner cerebral trauma and focal outer cerebral damage. The diffuse degeneration of cerebral white matter is associated with sagittal and lateral acceleration with centroaxial trauma and has a different pathogenesis from outer focal head trauma, typified by subdural hematomas and coup injuries. Unlike outer cerebral injury, over 50 percent of victims with diffuse axonal injury die within two weeks. These individuals characteristically have no lucid interval and remain unconscious, vegetative, or severely disabled until death. Compared to head trauma victims without diffuse axonal injury, there is a lower incidence of skull fractures, subdural hemorrhages, or other intracranial mass effect as well as outer brain contusions. Primary brainstem injuries often demonstrated at autopsy are seen in the reported victim. Diffuse axonal injury is produced by various angles of acceleration with prolonged acceleration/deceleration usually accompanying traffic accidents. Less severe diffuse axonal injury causes concussion.     

Administration of cyclophosphamide during late pregnancy and early lactation: a case report.

Burkitt lymphoma was diagnosed in a patient during the third trimester of pregnancy. Treatment with a low-dose, seven-day course of intravenous cyclophosphamide gave a good response which permitted the pregnancy to be carried to term, with delivery of a normal infant. When the mother received cyclophosphamide during lactation while the baby was breast-fed, the infant''s leukocyte and platelet counts were rapidly depressed. Results in this patient and a survey of reported cases in which cyclophosphamide was administered during pregnancy and lactation lead to the conclusions that (1) low-dose intravenous cyclophosphamide therapy is not hazardous to the fetus during late pregnancy; (2) mammary concentration of the drug is too toxic to the infant''s bone marrow; and (3) breast-feeding the baby should be suspended during the period the mother is receiving cyclophosphamide treatment.     

Paraplegia and congenital contractures as a consequence of intrauterine trauma

We present a newborn infant with paraplegia and contractures of the lower limbs, consistent with neurologic injury rather than malformation. The mother was involved in a severe motor vehicle accident during the sixth month of pregnancy. We propose that this infant's injuries are a result of that accident. © 1992 Wiley-Liss, Inc.     

Nystagmus induced by circular head shaking in normal human subjects

 We recorded three-dimensional eye and head movements during circular, horizontal, vertical, and torsional head shaking in six human subjects with normal vestibular function. With circular head shaking, the stimulation of the canals by the termination of the head movement is similar to that following a step in velocity about the naso-occipital axis. A large torsional nystagmus with slow phase eye velocity of about 20°/s was observed upon cessation of circular head shaking. The three-dimensional eye movements expected from stimulation of the semicircular canals by the head-shaking maneuvers were calculated. The predicted activation of the canals was determined by projecting the head velocity (in head coordinates) into the canal planes and then processing the signal with the transfer function of the canals. The torsional eye velocity components predicted by the stimulation of the canals matched the recorded ones. We observed small horizontal eye velocities that could not be predicted by the stimulation of the canals alone. No eye movements were observed after the end of head shaking about a fixed horizontal or vertical axis. The eye velocities following the termination of head oscillations in the roll plane were small. The analysis methods developed for this study may be useful in the investigation of eye movements elicited by other types of three-dimensional head movements. Received: 24 April 1997 / Accepted: 8 July 1998     

Maternal cradling and infant nipple preferences in rhesus monkeys (Macaca mulatta)

This study investigated lateral biases in nipple preferences, maternal cradling, carrying, and retrieval in 41 rhesus macaque (Macaca mulatta) mother–infant dyads living in two captive social groups. Observations were made during the first 6 weeks of infant life using a combination of scan sampling and ad-libitum sampling techniques. Infants exhibited a significant left-nipple preference in the first weeks of life but the bias decreased with infant age. Mothers showed a left-arm bias in carrying their infants but no significant lateral bias in cradling or retrieval. Our results suggest that the left-side cradling bias reported in studies of humans and some other primates reflects a bias in the infant's nipple preference rather than in maternal behavior. The infants' preference for the left nipple is consistent with both Salk's (1960) heartbeat hypothesis and with more recent hypotheses linking this lateral bias with brain asymmetry and hemispheric specialization for mother–infant communication. © 1998 John Wiley & Sons, Inc. Dev Psychobiol 32: 305–312, 1998     

The Mother,The Psychoanalyst,The Poet and The Artist: Containment and Growth of The Mind

This paper considers the difficulties which humans have in using and developing their capacity for thought. Growth of the human mind, through attunement of the mother's unconscious experience with the infant's, is explored along with the distortions which arise because of aversion to uncertainty and suffering. It then looks at psychoanalysis and the verbal and visual arts in the light of the maternal function, and the way in which they also promote the growth of the mind. Four products of the human mind – an excerpt from an infant observation published in 1998, some post‐Kleinian psychoanalytic clinical case material from the 1980s, John Keats's 19th century Ode to a Nightingale and Lucas Cranach's 1526 painting, Adam and Eve – are used to illustrate some of the similarities and differences among them in giving conscious form to the unconscious.     

Fenestration and duplication of the vertebral artery

The vertebral artery (VA) acts as a foundation for the posterior circulation of the head and neck. It presents a number of anomalies that can be easily visualized thanks to modern imaging techniques, such as MR and CT angiography or color Doppler ulrasonography. Determining the appropriate terminology for those anomalies can be sometimes more challenging than their recognition. One particular challenge concerns the differentiation betweenVA fenestration and duplication. Because of the different clinical prognoses associated with those anomalies, confusion should be avoided. Knowledge of the morphological anomalies associated with the VA is important for both radiologists and head and neck surgeons, because any injury to the VA can result in a threat to the vascular supply of the brain stem, the cerebral or cerebellar hemispheres, the thalamus, cervical nerve roots and particularly the lateral medulla (Wallenberg's syndrome). This article analyses world literature concerning the issue of VA fenestration and duplication to facilitate a differential diagnosis. Clin. Anat. 26:933–943, 2013. © 2013 Wiley Periodicals, Inc.     

Mother and infant smiling exchanges during face-to-face interaction in infants with and without Down syndrome

We examined social smiling in infants with and without Down syndrome, aged from 3.2 to 13.6 months old. They were videotaped during an episode of spontaneous face-to-face interaction and a subsequent mother's still-face situation. Results indicated that infants smiled longer in the spontaneous face-to-face episode than in the still-face episode, even though this result was only significant in typically developing infants. Typically developing infants also smiled for a longer period than Down's syndrome infants during the spontaneous interaction episode. Moreover, infant's smile preceded the onset of the mother's smile, but in 6.2- to 13.6-month-old typically developing infants, the probability of mothers smiling before infants increased. These findings emphasize the possible existence of differences in the development of facial expression from signs to social symbols between infants with and without Down syndrome. © 1997 John Wiley & Sons, Inc. Dev Psychobiol 31: 277–286, 1997     

Preaxial acrofacial dysostosis (Nager syndrome) associated with an inherited and apparently balanced X;9 translocation: Prenatal and postnatal late replication studies

We report on an infant with preaxial acrofacial dysostosis (Nager syndrome) who was diagnosed prenatally as having an apparently balanced X/autosome translocation [46,X,t(X;9)(p22.1;q32)mat] inherited from a previously diagnosed mosaic translocation carrier mother [46,XX/46,X,t(X;9)(p22.1;q32)]. Replication studies on amniocytes showed the normal X chromosome to be late replicating while the same studies repeated on the infant's lymphocytes showed the translocated X chromosome to be late replicating in most cells. Late replication studies of the mother's lymphocytes demonstrated that the normal X chromosome was late replicating in most cells. The presence of Nager syndrome in this infant may be the result of critical break-points and/or position effects on chromosome 9, inducing expression of a gene responsible for the syndrome. © 1993 Wiley-Liss, Inc.     

Digastric muscle of the kangaroo: A comparative anatomical study

Although the human digastric muscle is classified as a suprahyoid muscle, none of the digastric muscles in other mammals are classed as suprahyoid in textbooks of veterinary anatomy. The aim of this study was to describe the anatomical relationship of the digastric muscle in a marsupial, the kangaroo, and to consider factors thought to be important in leading to the different position of the muscle in quadrupeds compared with humans. Eight heads of the common wallaroo (Macropus robustus)were used in this study. They were fixed by injection of 10% formalin solution into the carotid arteries and dissected under a stereomicroscope. The digastric muscle in the common wallaroo arose from the paroccipital process of the temporal bone and inserted into the mandible but had no intermediate tendon or any connection with the hyoid bone. It was supplied by both the mandibular and facial nerves. The hyoglossus muscle attached to the inferior surface of the hyoid bone and its ventral border overlapped the mylohyoid muscle. The hypoglossal nerve passed between these two muscles. Therefore, in contrast to humans, the digastric, hyoglossus, and mylohyoid muscles in the kangaroo were all located inferior to the hyoid bone. Differences in head posture and the position of the larynx between kangaroos and humans may account for the observed difference in the digastric muscle's position relative to the hyoid bone between these species. Anat. Rec. 251:346–350, 1998. © 1998 Wiley-Liss, Inc.     

A case of broken bones and systems: The threat of irresponsible testimony

A 2‐month‐old healthy baby presented to the emergency room with an arm that was not moving and was found to have multiple and extensive fractures of her long bones. An extensive medical work‐up was done, and the hospital's multidisciplinary child abuse team was consulted, including child protection, genetics, radiology, and general pediatrics. It was determined that the history, clinical findings, radiographic findings, and laboratory findings were consistent with child abuse. Child protection services removed the child from the home, and for the next 10 months, the infant was well, and did not sustain a single new fracture. At a civil proceeding to determine the infant's custody, an expert witness for the defense concluded that the child had hypermobile Ehlers‐Danlos syndrome and low vitamin D. He stated that because of these conditions, the baby was vulnerable to fractures with routine handling. This is a personal story of a clinical geneticist who explored fracture fact versus fracture fiction and learned about the difference between responsible and irresponsible testimony. This story gives insight into how physicians can prepare to transition from the clinic to the courtroom. It is also a story about how medical experts must and should remain unbiased, evidence‐based, and committed to accuracy and truth.     

Mutation screening of the dopamine D1 receptor gene in tourette's syndrome and alcohol dependent patients

We report a single stranded conformational polymorphism (SSCP) analysis of the coding region of the dopamine D1 receptor (DRD1) in Tourette's syndrome (n = 50) and control (n = 50) subjects. Tourette's syndrome populations with comorbidity for attention deficit-hyperactivity disorder (AD-HD) (n = 35) and obsessive compulsive disorder (OCD) (n = 30) were also screened. As a related study, we also screened patients diagnosed with alcohol dependence (n = 72). The present study discovered no DRD1 coding region mutations in any of the Tourette's syndrome or alcohol dependent patients. One silent mutation, a C for a T at Ile49, was discovered in one control subject. The non-polymorphic structure of the DRD1 gene among the Tourette's syndrome, Tourette's syndrome comorbid with AD-HD and OCD and the alcohol dependent populations screened by SSCP suggests that coding region mutations of the DRD1 gene are unlikely to contribute to the inheritance of these disorders. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 81:241–244, 1998. © 1998 Wiley-Liss, Inc.     

Severe limb abnormalities: Nievergelt or new syndrome?

Since the characteristic mesomelic limb abnormalities of the autosomal-dominant Nievergelt syndrome (NS) may be casually nonspecific, we are unsure whether our patient with these abnormalities but also with severe, symmetrical hand and foot anomalies has an unusual form of Nievergelt syndrome or a previously apparently undescribed syndrome. This infant's condition could represent an autosomal-dominant new mutation, or an autosomal or X-linked recessive disorder. Am. J. Med. Genet. 70:48–51, 1997. © 1997 Wiley-Liss, Inc.     

A computerized decision support system to predict the variations in the cerebral blood flow of mechanically ventilated infants

A computerized decision support system is described to predict the changes in the cerebral blood flow (CBF) of mechanically ventilated infants in response to different ventilatory settings. A CBF controller was developed and combined with a mathematical model of the infant's respiratory system to simulate the effects of ventilatory settings on the infant's CBF. The performance of the system was examined under various ventilatory treatments and the results were compared with available experimental data. The comparisons showed good agreement between the simulation results and experimental data for preterm infants. These included the results obtained under conditions of hypoventilation, hyperventilation, hypoxia, and hyperoxia. The presented decision support system has the potential to be used as an aide to the intensivist in choosing appropriate ventilation treatments for infants to prevent the untoward consequences of hazardous changes in CBF in mechanically ventilated infants such as hypoxic-ischemic brain injuries.     

Accidental traumatic head injury in infants and young children

Abstract This article will discuss accidental head injuries in infants and young children. The first category of injury is the crushing head injury. Static forces applied slowly to the head result in multiple fractures of the skull and contusions and lacerations of the brain resulting from the bone fragments striking the brain. This article will discuss the subject of short falls in young children and the resulting head injuries. Because falls are frequent events in early life, many cases have been collected and many papers written on the subject. Study of these cases is informative about the injuries likely to occur in these falls. Most often, only a minor contact injury such as scalp bruise or laceration results. In a 2 to 3% of falls, a simple linear skull fracture occurs and the majority of these are uneventful in terms of neurological deficit or intracranial bleeding. In about 1% of the fractures, an epidural or subdural hemorrhage occurs. Each of these forms of contact hemorrhages will be discussed and illustrated. While these are relatively rare injuries, it is essential that they can be identified as consistent with an accidental mechanism so that an erroneous diagnosis of inflicted injury is not made.     

Stroke: Anatomy of a catastrophic event

Subarachnoid hemorrhage (SAH) resulting from the rupture of a cerebral aneurysm represents one major cause of stroke. SAH may be followed by a spontaneous severe contraction of major cerebral arteries, a condition referred to as cerebral vasospasm. Vasospasm may result in brain ischemia or actual tissue death. This constrictive vascular state is devastating, remains largely untreatable, and is a major cause of morbidity and mortality in SAH patients. Approximately 30,000 Americans are affected by this condition each year. The overall death rates are 25%, and significant neurological complications occur in 50% of individuals who survive the initial bleed. This report highlights some of the important aspects of this vascular disease. Anat. Rec. (New Anat.) 253:58-63, 1998. © 1998 Wiley-Liss, Inc.